Hepatic Metabolism of Perfluorinated Carboxylic Acids: A Nuclear Magnetic Resonance Investigation in Vivo
Final technical rept. 15 Feb 1990-14 Dec 1994
WRIGHT STATE UNIV DAYTON OH
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This report outlines our progress regarding toxicological studies of perfluoro- n-octanoic acid PFOA and perfluoro-n-decanoic acid PFDA. These Air Force chemicals belong to a class of compounds known as peroxisome proliferators PP. Many PP cause hepatotoxicity and carcinogenesis in rodents. The mechanisms are unknown and represent an active area of research. Recent studies have demonstrated specific effects of PFDA treatment on hepatic phospholipid and carbohydrate metabolism. PFDA alters hepatic glucose transport. PFDA-treated rats showed rates of glucose transport which were 2-fold less than controls. PFDA treatment also caused a 3-fold increase in liver diacylglycerol DAG PFOA had no effect. This DAG is derived from phosphatidylcholine via phospholipase C activity. Since DAG stimulates protein kinase C PKC, these data suggest that the hepatotoxic effects of PFDA may be initiated through a PKC response. Accordingly, experiments are in progress to investigate the effects of PFDA on liver PKC activity preliminary data are presented herein. In other studies, preliminary data indicate that the influence of PFDA on phospholipid metabolism occurs at doses well below the LD50. Also, in studies involving C8-C11 perifluoro- carboxylic acids, only chain lengths C9 affect phospholipid metabolism. These data suggest that the metabolic effects may be related to the compounds ability to diffuse into membranes. This research furthers our understanding of the mechanisms involved in the hepatotoxicity associated with these Air Force chemicals.
- Medicine and Medical Research